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Correlation of Matrisome-Associatted Gene Expressions with LOX Family Members in Astrocytomas Stratified by IDH Mutation Status

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Autor(es):
Laurentino, Talita de Sousa ; Soares, Roseli da Silva ; Marie, Suely Kazue Nagahashi ; Oba-Shinjo, Sueli Mieko
Número total de Autores: 4
Tipo de documento: Artigo Científico
Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 17, p. 20-pg., 2022-09-01.
Resumo

Tumor cell infiltrative ability into surrounding brain tissue is a characteristic of diffusely infiltrative astrocytoma and is strongly associated with extracellular matrix (ECM) stiffness. Collagens are the most abundant ECM scaffolding proteins and contribute to matrix organization and stiffness. LOX family members, copper-dependent amine oxidases, participate in the collagen and elastin crosslinking that determine ECM tensile strength. Common IDH mutations in lower-grade gliomas (LGG) impact prognosis and have been associated with ECM stiffness. We analyzed the expression levels of LOX family members and matrisome-associated genes in astrocytoma stratified by malignancy grade and IDH mutation status. A progressive increase in expression of all five LOX family members according to malignancy grade was found. LOX, LOXL1, and LOXL3 expression correlated with matrisome gene expressions. LOXL1 correlations were detected in LGG with IDH mutation (IDHmut), LOXL3 correlations in LGG with IDH wild type (IDHwt) and strong LOX correlations in glioblastoma (GBM) were found. These increasing correlations may explain the increment of ECM stiffness and tumor aggressiveness from LGG-IDHmut and LGG-IDHwt through to GBM. The expression of the mechanosensitive transcription factor, beta-catenin, also increased with malignancy grade and was correlated with LOXL1 and LOXL3 expression, suggesting involvement of this factor in the outside-in signaling pathway. (AU)

Processo FAPESP: 16/05777-1 - Papel funcional da enzima LOXL3 em astrocitomas
Beneficiário:Talita de Sousa Laurentino
Modalidade de apoio: Bolsas no Brasil - Mestrado
Processo FAPESP: 15/03614-5 - Detalhamento funcional do papel de CD99 em astrocitomas
Beneficiário:Sueli Mieko Oba Shinjo
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 21/01207-4 - Análise do papel funcional de LOXL3 em glioblastoma
Beneficiário:Talita de Sousa Laurentino
Modalidade de apoio: Bolsas no Brasil - Doutorado